Steno‐sphere: Navigating the enigmatic world of emerging <scp>multidrug‐resistant</scp><i>Stenotrophomonas maltophilia</i>

Coyne, Ashlan J Kunz; Herbin, Shelbye R; Caniff, Kaylee E; Rybak, Michael J.

doi:10.1002/phar.2828

Cited by 3 publications

(2 citation statements)

References 106 publications

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“…Stenotrophomonas is a diverse genus of Gram-negative γ-proteobacteria that includes opportunistic pathogens ( 1 , 2 ). S. indicatrix strains have been reported to degrade phenanthrene ( 3 ).…”

Section: Announcementmentioning

confidence: 99%

Draft genome sequences of five Stenotrophomonas indicatrix strains isolated from soil

Żur-Pińska,

Sharma,

Hay

2024

Microbiol Resour Announc

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Section: Announcementmentioning

confidence: 99%

Draft genome sequences of five Stenotrophomonas indicatrix strains isolated from soil

Żur-Pińska,

Sharma,

Hay

2024

Microbiol Resour Announc

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“…S. maltophilia has also significantly infected coronavirus disease of 2019 (COVID-19) patients ( 11 , 12 ). S. maltophilia infections are often difficult to treat due to the multi-drug-resistant nature of associated strains ( 13 – 15 ). To survive in its various niches, S. maltophilia utilizes biofilm formation and a range of surface and secreted factors, including flagella, siderophore, and enzymes secreted by a type II secretion system ( 16 – 26 ).…”

Section: Introductionmentioning

confidence: 99%

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Cobe,

Dey,

Minasov

et al. 2024

mBio

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Stenotrophomonas maltophilia expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A S. maltophilia mutant lacking the gene for 20845 was impaired for killing Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa . Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant E. coli being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede E. coli , indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the S. maltophilia T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase. IMPORTANCE Stenotrophomonas maltophilia is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to S. maltophilia infection. In hospital water systems and various types of infections, S. maltophilia co-exists with other bacteria, including other pathogens such as Pseudomonas aeruginosa . We previously demonstrated that S. maltophilia has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, S. maltophilia currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).

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Treatment approaches for severe Stenotrophomonas maltophilia infections

Mojica,

Bonomo,

van Duin

2023

Current Opinion in Infectious Diseases

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Purpose of review Stenotrophomonas maltophilia is an emerged opportunistic pathogen. Intrinsic multidrug resistance makes treating infections caused by S. maltophilia a great clinical challenge. Herein, we provide an update on the most recent literature on treatment options for severe S. maltophilia infections. Recent findings Trimethoprim-sulfamethoxazole (SXT) is recognized as the first-line therapy for S. maltophilia infections. However, its clinical use is based on good in vitro activity and favorable clinical outcomes, rather than on solid minimum inhibitory concentration (MIC) correlations with pharmacokinetic/pharmacodynamics (PK/PD) and/or clinical outcomes. The same is true for other treatment options like levofloxacin (LVX) and minocycline (MIN). Recent PK/PD studies question the current clinical breakpoints for SXT, LVX, and MIN. Based on this, the latest guidance issued by the Infectious Diseases Society of America (IDSA) recommends using these agents only as part of a combination therapy. Alternatively, novel therapeutic options such as cefiderocol (FDC) and ceftazidime-avibactam plus aztreonam (CZA-ATM) are suggested, based on limited but promising clinical data. Summary PK/PD data and controlled clinical studies are needed to optimize current treatment options. Presently, combination therapy of SXT, LVX, MIN, or FDC, or monotherapy with CZA-ATM are recommended therapeutic options for severe-to-moderate S. maltophilia infections.

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Steno‐sphere: Navigating the enigmatic world of emerging multidrug‐resistantStenotrophomonas maltophilia

Cited by 3 publications

References 106 publications

Draft genome sequences of five Stenotrophomonas indicatrix strains isolated from soil

Draft genome sequences of five Stenotrophomonas indicatrix strains isolated from soil

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Treatment approaches for severe Stenotrophomonas maltophilia infections

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